南方农业学报2025，Vol.56Issue(1)：314-323,10.DOI:10.3969/j.issn.2095-1191.2025.01.028
N-乙酰半胱氨酸缓解小鼠代谢综合征膀胱纤维化的分子机制
Molecular mechanism of N-acetylcysteine alleviating bladder fibrosis in mice with metabolic syndrome
摘要
Abstract
[Objective]To explore the molecular mechanism by which N-acetylcysteine(NAC)alleviated bladder fi-brosis in metabolic syndrome mice,which could provide theoretical reference for a deeper understanding of the pathologi-cal process of bladder fibrosis and the development of new treatment strategies.[Method]C57BL/6 male mice and ob/ob(B6.V-Lepob/J)male mice(metabolic syndrome model)at 8 weeks of age were selected.The experiment lasted for 20 weeks.After the end of the experiment,the mice were killed and the bladder tissues were collected.C57BL/6 male mice were used as the control group(Con),and ob/ob(B6.V-Lepob/J)male mice were used as the metabolic syndrome model group(ob/ob).The relative expression levels of TGF-β1,SMAD,p38,p-ERK,p-JNK,α-SMA,3-Nitrotyrosine(NT)and other proteins in the bladder tissues of mice were detected by Western blotting.Immunohistochemical staining was used to detect the expression and distribution characteristics of NF-κB and TGF-β1 in the bladder tissues of mice.Mouse bladder smooth muscle cells(BSMCs)were isolated,the glucose concentration was screened and the growth curve of BSMCs was drawn.The control group(Con),high glucose group(HG),high glucose+NAC group(HG+NAC)and hyperos-motic group(HO)were set up to detect the relative expression levels of CRP,IL-6,IL-1β,NLRP3,TGF-β1,BK-β1 and SKCa3 proteins.MCC950 and PDTC were used to inhibit the NLRP3 and NF-κB signaling pathways,and the relative ex-pression levels of ROCK1,NLRP3,NF-κB and TGF-β1 proteins were detected.[Result]Compared with the Con group,the relative expression of NT,TGF-β1 and α-SMA proteins in the bladder tissue of the ob/ob group mice was signifi-cantly increased(P<0.05,the same below),and there was no significant difference in the relative expression of SMAD,p38,p-ERK and p-JNK proteins(P>0.05,the same below).The results of glucose concentration screening showed that 45 mmol/L glucose was the optimal intervention concentration.Western blotting results showed that compared with the Con group,the relative expression of CRP,IL-6,TGF-β1,IL-1β and NLRP3 proteins in BSMCs of the HG group was signifi-cantly increased,and the relative expression of BK-β1 and SKCa3 proteins was significantly decreased.Compared with the HG group,the relative expression of CRP,IL-6,TGF-β1,IL-1β and NLRP3 proteins in BSMCs of the HG+NAC group was significantly decreased,and the relative expression of BK-β1 and SKCa3 proteins was significantly increased.After in-hibiting the NLRP3 and NF-κB signaling pathways,compared with the HG group,the relative expression of TGF-β1 pro-tein in BSMCs of HG+MCC950 and HG+PTCD groups was significantly decreased,and the relative expression of NF-κB protein was significantly increased;the relative expression of ROCK1 and NLRP3 proteins in BSMCs of HG+MCC950 group was significantly decreased,and there was no significant difference in the relative expression of ROCK1 and NLRP3 proteins in BSMCs of HG+PTCD group.[Conclusion]High glucose-induced bladder function damage in mice involves molecular mechanism pathways related to oxidative stress-inflammatory response-tissue fibrosis.NAC mainly blocks the development of oxidative stress,inflammatory response and fibrosis in functional damage by inhibiting the ROS/NLRP3/NF-κB/TGF-β1 signaling pathway.Compared with anti-inflammatory treatment,NAC antioxidant treat-ment may have a more significant therapeutic effect on tissue fibrosis.关键词
N-乙酰半胱氨酸/代谢综合征/膀胱功能损害/氧化应激/炎症反应Key words
N-acetylcysteine/metabolic syndrome/bladder function damage/oxidative stress/inflammatory re-sponse分类
农业科技引用本文复制引用
任亚琳,苏博严,何綦琪..N-乙酰半胱氨酸缓解小鼠代谢综合征膀胱纤维化的分子机制[J].南方农业学报,2025,56(1):314-323,10.基金项目
国家自然科学基金项目(81800671,82360156) （81800671,82360156）
甘肃省卫生健康行业科研管理项目(GSWSKY2021-070) （GSWSKY2021-070）
兰州大学萃英人才面上项目(CY2021-MS-A02) National Natural Science Foundation of China(81800671,82360156) （CY2021-MS-A02）
Gansu Health Care In-dustry Research Management Project(GSWSKY2021-070) （GSWSKY2021-070）
Lanzhou University Cuiying Talent Top Project(CY2021-MS-A02) （CY2021-MS-A02）
